Infectious Disease

The numbers of certain tick-borne diseases in the United States reported to the CDC have risen within the past decade. But the essential question remains as to whether these increases are attributable to improved recognition and reporting or if they are rising due to other factors.

In the past 10 years, the following tick-borne diseases have evolved as the top five reported in the United States: Lyme disease (about 35,000 reported cases yearly); Rocky Mountain spotted fever (RMSF; about 2,500 cases reported yearly); ehrlichiosis and anaplasmosis (about 1,000 cases per year each); and babesiosis (about 250 cases reported yearly), according to Lyle R. Petersen, MD, MPH, director of the division of vector-borne diseases at the CDC in Fort Collins, Colo., and a member of the Infectious Disease News Editorial Board.

Eugene D. Shapiro, MD, professor of pediatrics, epidemiology and investigative medicine at Yale University, said that most cases of babesiosis go undiagnosed.

Photo courtesy of Shapiro ED

“They’re all becoming much more common,” Petersen told Infectious Disease News. “The incidence of each has increased in recent decades and particularly during the last 10 years. Lyme disease, babesiosis and anaplasmosis all have the same vector, Ixodes scapularis ticks, which would explain why they’re all going up in tandem.”

Infectious disease experts have attributed these increases to improved reporting and diagnosis, along with other factors.

“The other reason postulated recently is to do with climate changes,” said Sunil K. Sood, MD, infectious diseases specialist at Cohen Children’s Medical Center of New York, director of pediatrics at Southside Hospital and professor of pediatrics and family medicine at Hofstra North Shore-LIJ School of Medicine in New Hyde Park, N.Y. “It looks like we are getting expanded ranges for tick vectors, but it could also be better diagnostic assays, improved reporting, improved awareness among physicians, improved state and local surveillance for tick-borne diseases — all of these factors lead to increases over time.”

Reported cases

Henry M. Feder Jr.

“Does it really change or do we notice it more?” said Henry M. Feder Jr., MD, professor of pediatrics and family medicine at University of Connecticut Health Center and Connecticut Children’s Medical Center. “When these things get publicity, doctors are diagnosing them when they didn’t diagnose it beforehand. For example, patients with Lyme disease in 1976 were not recognized at all because doctors didn’t know what it was. … As these things may change, a question will be, have they increased or are they just being shown now that doctors have learned to recognize them?”

Origins of increase

Petersen said there is more to the increases than just better recognition.

“We believe they are all truly increasing in incidence, and there’s a variety of reasons for that,” he said. “For Lyme disease, babesiosis and anaplasmosis, we believe that the number of ticks is increasing, largely due to the fact that deer populations are markedly increasing. This has been a trend over 5 decades now.”

He also said more people are living in and traveling to rural areas, where these ticks are present. In 2005, Brownstein and colleagues used a climate suitability model of the I. scapularis tick to examine the effects of climate change on Lyme disease risk. They predicted that the ticks will expand north into Canada with a 213% increase in suitable habitat by the 2080s; they also predicted that the ticks will retract from the South and move more into the Central states.

Besides climate changes, Sood said some evidence has also shown that a rise in nighttime temperature in the Northern latitudes has correlated with an increase in tick and mosquito populations.

Preventive measures

Preventive techniques and diagnostic tools are available. Although a Lyme disease vaccine (LYMErix, GlaxoSmithKline) was available in the United States from 1998 until 2002, no vaccines are currently available for tick-borne diseases in the United States.

A vaccine for tick-borne encephalitis is available in Europe and in Canada for those traveling to Europe. However, the vaccine is not licensed in the United States.

“The number of people who need to be vaccinated or should be vaccinated is relatively small, and it’s just not economically feasible for a vaccine manufacturer to get that vaccine licensed here in the United States,” Petersen said.

Physicians can suggest other preventive techniques to children and their parents. Specifically with the I. scapularis ticks, Petersen reiterated the CDC recommendations to wear long sleeves and long pants and to tuck pant legs into socks, although he said this may be unrealistic, especially during the summer. Most importantly, physicians should advise children and their parents to shower or bathe immediately after outdoor exposure. 

Lyle R. Petersen

“The most important thing is to recognize the ticks when they’re on the child’s body or the adult’s body, and remove them, which will largely reduce the risk for transmission if caught early — within a day after the tick has attached,” Petersen said.

The CDC also recommends the use of repellants that contain 10% to 30% of DEET in children aged 2 months and older.

Preventive measures can also be taken in the environment by spraying pesticides around the perimeter of yards or by using bait boxes. “The most reasonable thing is to keep grass cut short and to keep a barrier [with mulch] between the woods and the lawn,” Feder said.

However, Petersen said: “All of these methods have uncertain or unknown efficacy in real life. We know that theoretically they should work, but we don’t have any controlled trials.”

The CDC is conducting large community intervention trials to determine what methods actually reduce illnesses contracted from I. scapularis ticks. Researchers are also examining the development of more environmentally friendly control measures.

Diagnosis and treatment

It is known, at least regarding Lyme disease, that it takes a while for disease to develop after a tick bite. In the case that preventive measures do not work and children present with a tick bite, “prompt removal of the tick can potentially reduce the risk for illness by doing tick checks,” Petersen said. “We don’t really have similar kinds of data for the rest of these diseases, but they’re probably similar.”

Regarding Lyme disease, misinformation, inappropriate testing and inappropriate treatment run rampant, according to Petersen.

“We hear from a lot of physicians that they are confronted with patients with strange Lyme disease tests they never heard of or tests that were administered inappropriately, and people wonder what to do,” he said.

He said physicians should administer the enzyme-linked immunosorbent assay test before the Western blot; many patients are being tested without this first test in the two-tiered algorithm and that has led to many false-positives.

“A final problem is that physicians need to think about who they are testing because any diagnostic test, no matter how good it is, will have a certain number of false-positives, and the number of false-positives goes up if patients with low pretest likelihood of having the disease are tested,” Petersen said.

Currently, the CDC is conducting research that aims to increase the sensitivity of the serological tests currently in use for RMSF.

“For Lyme disease, while the recommended testing works quite well, the ease and specificity of the testing are not perfect,” Petersen said. “We’d like to develop tests that are easier to use and are subject to fewer false-positives.”

Sood recommended certain steps to follow when a patient presents with a tick bite. First, confirm that what the patient brought in is in fact a tick, identify it, and then determine how long the tick was attached. He and colleagues published a 1997 study in the Journal of Infectious Diseases that revealed ticks attached for less than 72 hours were not likely to cause infection. Moreover, many submissions were not ticks at all, he said, but instead insects or artifacts.

“Base your consideration of antibiotic prophylaxis on those three facts (whether it’s a tick, identification of the tick species, and duration of attachment) and not on trying to test the ticks for the spirochete, because it can be misleading and can lead to overtreatment,” Sood said.

Treatment for the top five tick-borne diseases includes amoxicillin and doxycycline for Lyme disease and doxycycline for ehrlichiosis, anaplasmosis and RMSF. Babesiosis is usually treated with atovaquone (Mepron, GlaxoSmithKline) plus azithromycin or, in cases of severe illness, with clindamycin and quinine (Qualaquin, AR Holding Co.).

“Doxycycline, with the exception of babesiois, at least for these common tick-borne illnesses is kind of one-stop shopping for antibiotic therapy,” Petersen said.

He cautioned against the notion of avoiding doxycycline in children aged younger than 8 years because of potential dental stains. This avoidance has led to delayed or inappropriate treatment of RMSF, ehrlichiosis and anaplasmosis, and even to fatalities or additional morbidity, Petersen said.

“What’s important to know — and this needs to be reinforced — is that dental staining at the recommended dose and duration needed to treat these diseases has not been shown to cause staining of permanent teeth, and so doxycycline, if these diseases are suspected, should be administered if there is no other major contraindication,” Petersen said.

Disease presentation

In many cases, tick-borne diseases present as a febrile nonspecific illness and often times resolve without treatment. Babesiosis, anaplasmosis and ehrlichiosis, for example, are characterized acutely by fever.

“When the fever breaks, your body has cleared it,” Feder said.

“Children’s immunity may be better and sometimes they clear the infection on their own,” Sood said. “A teaching point is to always include these diseases in the differential diagnosis of febrile nonspecific illnesses, especially between the spring and the fall.”

Often times, Sood said, laboratory tests, including serology and polymerase chain reaction, are the clue to diagnosis. However, Shapiro said, in most cases of babesiosis, a diagnosis is never made.

“However, if you’re immunocompromised, if you don’t have a spleen, for example, or if you’re on immunosuppressants, it can cause very severe symptoms that can be life-threatening,” said Shapiro, an Infectious Disease News Editorial Board member.

Children infected with anaplasmosis tend not to get as sick as adults with the disease. “If you do serosurveys in endemic areas, you’ll find that there have been kids who have been infected but never knew it,” Shapiro said, adding that some patients get sicker from anaplasmosis, with low white blood cell count and low platelet counts, although it is uncommon.

RMSF and ehrlichiosis, found in the southern United States, result in more severe illness than anaplasmosis or babesiosis. RMSF can cause meningitis and has a “significant” mortality rate if not treated, Shapiro said.

Because people are concerned with long-term infection of Lyme disease, Petersen said the CDC is also looking into tests that can distinguish current infection from previous infection.

“Some people who do get Lyme disease have persistent syndromes even after treatment, and we don’t know the cause,” he said. “Trying to figure out what is causing it, characterizing it and figuring out how to treat it is a priority.” – by Tina DiMarcantonio

References:

• Bacon RM. MMWR Surveill Summ. 2008;57:1-9.
• Brownstein JS. Ecohealth. 2005;2:38-46.
• CDC. MMWR Morb Mortal Wkly Rep. 2011;58:1-100.
• Dahlgren FS. Am J Trop Med Hyg. 2011;85:124-131.
• Feder HM Jr. Clin Infect Dis. 2011;53:e142-146.
• Openshaw JJ. Am J Trop Med Hyg. 2010;83:174-182.
• Sood SK. J Infect Dis. 1997;175:996-999.

Disclosures:

• Drs. Feder, Petersen, Shapiro and Sood report no relevant financial disclosures.

Are the reported increases in the incidence of some tick-borne diseases due to better reporting and recognition, or are they true increases in disease?

Increases are due to both reasons.

Increases in incidence in tick-borne diseases are due to both true increases in disease risk and also better reporting and recognition. We know from a number of extensive field studies and modeling papers that ticks that transmit these pathogens are expanding in their ranges. There are historical and ongoing landscape changes that account for this and a lot of interest in climate change as well. All of that contributes to changes in tick-borne disease risk and in the picture of incidence that we see. 

Anne Gatewood Hoen

But also, our understanding of the distribution and determinants of tick-borne diseases has improved recently. That has allowed for better reporting and recognition because the public is now aware of tick-borne diseases, and physicians and public health officials know what to look for and know where to look in terms of incident cases. However, that is not always straightforward in such a dynamic system that we’re seeing spread into new areas.

Unfortunately, we don’t have a lot of great ways to prevent and control tick-borne diseases, so reversing this trend of increasing incidence is a major challenge.

Anne Gatewood Hoen, PhD, is an instructor of community and family medicine at Dartmouth Medical School in Lebanon, N.H. Disclosure: Dr. Hoen reports no relevant financial disclosures.

Unlikely that both hypotheses are true concurrently.

Tick-borne illnesses pose real problems for pediatricians, not to mention the patients suffering from those illnesses. I suspect that both postulates are true: There are truly more cases of illness, and better reporting and recognition also contribute to documented increases. However, in any one location, both factors are unlikely to concurrently apply. As the primary reservoir hosts, as well as primary vectors of these diseases spread geographically, illness may appear in areas where practitioners are less alert to common presentations. Practitioners soon learn, and as the geographic areas are usually contiguous, this awareness is likely measurable in a relatively short period of time. Unusual presentations of disease become more understood in those areas of highest prevalence, and that knowledge spreads more slowly to adjacent areas. Our recent investment in public health reporting infrastructure probably also helps in both more rapid recognition and reporting.

William T. Gerson

From a primary care viewpoint, recognition of tick-borne illnesses — babesiosis, ehrlichiosis, Lyme disease, relapsing fever, tularemia, Rocky Mountain spotted fever — requires heightened vigilance, awareness of the wide scope of symptoms, and a commitment to taking a complete history and careful physical examination. I suspect from seroprevalence data that we all miss many cases. However, much of illness and most “missed” cases are likely due to mild or asymptomatic infection. We likely pursue due diligence when symptoms are intense or prolonged, or in endemic areas when rapid treatment prevents serious outcomes. Distinguishing those illnesses from presumed viral illnesses when the degree of symptoms or severity of outcomes is not out of the ordinary is both unlikely and unnecessary. More often, we are likely to be involved when patients with chronic symptoms (eg, abdominal pain, fatigue, headache) see practitioners who order serology that is either falsely positive or reflective of past exposure and who then embark on unnecessary treatment odysseys.

Our real challenge is education centered on recognition of tick-borne illnesses, first emphasizing common presentations and diagnostic testing and those requiring rapid, active management and then elaborating the more humbling, but certainly interesting, full spectrum of pathophysiology.

William T. Gerson, MD, is a clinical professor of pediatrics at the University of Vermont College of Medicine. Disclosure: Dr. Gerson reports no relevant financial disclosures.